miRNAs have emerged as post-transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Cdc42, one of the best characterized members of the Rho GTPase family, is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. In the present study, we have identified miR-137 as a potential regulator of Cdc42 expression. A bioinformatics search revealed a putative target-site for miR-137 within the Cdc42 3 0 UTR at nt 792-798, which is highly conserved across different species. Expression of miR-137 in colorectal cancer cell lines was found inversely correlated with Cdc42 expression. miR-137 could significantly suppress Cdc42 3 0 UTR luciferase-reporter activity, and this effect was not detectable when the putative 3 0 UTR target-site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced both mRNA and protein expression levels of Cdc42 and mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest, and blocking invasion of the colorectal cancer cells, whereas anti-miR-137 expression led to the opposite effect. Furthermore, expression of miR-137 suppressed the immediate downstream effector of Cdc42, PAK signaling. Our results suggest that miR-137 may have a tumor suppressor function by directly targeting Cdc42 to inhibit the proliferation and invasion activities of colorectal cancer cells. They raise an interesting possibility that Cdc42 activity and function can be controlled by miRNAs in addition to the classic regulators such as guanine nucleotide exchange factors and GTPase-activating proteins.
Single photon emission computed tomography (SPECT) myocardial perfusion imaging has attained widespread clinical acceptance as a standard of care for patients with known or suspected coronary artery disease. A significant contribution to this success has been the use of computer techniques to provide objective quantitative assessment in interpreting these studies. We have implemented the Emory Cardiac Toolbox (ECTb) as a pipeline to distribute the software tools that we and others have researched, developed, and validated to be clinically useful so that diagnosticians everywhere can benefit from our work. Our experience has demonstrated that integration of all software tools in a common platform is the optimal approach to promote both accuracy and efficiency. Important attributes of the ECTb approach are (1) our extensive number of normal perfusion databases for SPECT and positron emission tomography (PET) studies, each created with at least 150 patients; (2) our use of Fourier analysis of regional thickening to ensure proper temporal resolution and to allow accurate measurement of left ventricular function and dyssynchrony; (3) our development of PET tools to quantify myocardial hibernation and viability; (4) our development of 3-dimensional displays and the use of these displays as a platform for image fusion of perfusion and computed tomography angiography; and (5) the use of expert systems for decision support. ECTb is an important tool for extracting quantitative parameters from all types of cardiac radionuclide distributions. ECTb should continue to play an important role in establishing cardiac SPECT and PET for flow, function, metabolism, and innervation clinical applications.
BackgroundIn the field of acupuncture research, the topic of acupoint specificity has received increasing attention, but no unified conclusion has been reached on whether or not acupoint specificity exists. Furthermore, the majority of previous acupuncture neuroimaging studies have been performed using healthy subjects. In this study, patients with migraine were used to investigate acupoint specificity.MethodsThirty patients with migraine were enrolled and randomized into three groups: Traditional Acupuncture Group (TAG), Control Acupuncture Group (CAG), and Migraine Group (MG). The TAG was treated by acupuncture stimulation at Waiguan (TE5), Yang Lingquan (GB34), and Fengchi (GB20). The CAG was treated at Touwei (ST8), Pianli (LI6), and Zusanli (ST36). The MG received no treatment. Positron emission tomography with computed tomography (PET-CT) was used to test for differences in brain activation between the TAG and CAG versus MG, respectively.ResultsTraditional acupuncture treatment was more effective for pain reduction than control acupuncture treatment. The TAG showed higher brain metabolism than the MG in the middle temporal cortex (MTC), orbital frontal cortex (OFC), insula, middle frontal gyrus, angular gyrus, post-cingulate cortex (PCC), the precuneus, and the middle cingulate cortex (MCC). Metabolism decreased in the parahippocampus, hippocampus, fusiform gyrus, postcentral gyrus, and cerebellum in the TAG compared with the MG. In the CAG, metabolism increased compared with the MG in the MTC, supratemporal gyrus, supramarginal gyrus, and MCC, whereas metabolism decreased in the cerebellum.ConclusionsAcupuncture stimulation of different points on similar body regions in migraine patients reduced pain and induced different levels of cerebral glucose metabolism in pain-related brain regions. These findings may support the functional specificity of migraine- treatment-related acupoint.Trial registrationThe number of our clinical trial registration is: ChiCTR-TRC-11001813, and the protocol and inclusion criteria have already been registered as ChiCTR-TRC-11001813.
Objective The aim of this study was to assess the efficacy and safety of acupuncture in the treatment of patients with stable angina pectoris. Methods A literature search was performed in nine databases, including PubMed and the Cochrane Library, from their inception to 30 August 2018. Randomized controlled trials that compared acupuncture therapy with sham acupuncture or no treatment were included. Two reviewers under the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines assessed the eligibility of each record and extracted essential information independently. The data were merged using a fixed-effect model. Results Pooled analysis of 17 eligible trials with 1516 participants showed that acupuncture was associated with reduced angina attack frequency (–4.91; 95% confidence interval, –6.01– –3.82; p < 0.00001) and improved depression (–1.23; 95% confidence interval, –1.47– –1.00; p < 0.00001) and anxiety level (–0.96; 95% confidence interval, –1.16– –0.75; p < 0.00001) relative to sham treatment or standard care alone. No increased risk of adverse events was observed during treatment (relative risk, 0.70; 95% confidence interval, 0.33–1.48; p = 0.35). No significant improvement was shown in nitroglycerin use or angina intensity. The included studies were associated with unclear to high risk of selection or performance bias, and the quality of evidence was low to moderate. Conclusions Acupuncture may safely and effectively improve physical restrictions, emotional distress, and attack frequency in patients with stable angina pectoris. However, angina intensity and medication use were not reduced. Studies with adequate blinding and a valid sham control group are still warranted due to the current low quality of evidence.
We here retrospectively report the largest Chinese cohort of AD-HIES patients with STAT3 mutation. Unique features, when compared to existing literature reports, include (1) later age of diagnosis, (2) significantly higher rate of BCG complications, and (3) lower rate of candidiasis and chronic otitis media.
LncRNA HAND2-AS1 is characterized as a tumor suppressor involved in several types of malignancies, but its role in non-small cell lung cancer (NSCLC) is unknown. Our study was carried out to investigate the involvement of lncRNA HAND2-AS1 in NSCLC. In our study, we observed that levels of HAND2-AS1 were lower in tumor tissues than that in adjacent healthy tissues. Compared with healthy controls, plasma levels of HAND2-AS1 were lower, while levels of transforming growth factor β (TGF-β) were higher in NSCLC patients. A significant negative correlation between plasma levels of HAND2-AS1 and TGF-β1 was found in NSCLC patients but not in healthy controls. LncRNA HAND2-AS1 overexpression inhibits, while exogenous TGF-β1 treatment promotes cell migration and invasion ability and cancer cell stemness. Cancer cells with lncRNA HAND2-AS1 overexpression showed down-regulated TGF-β1, while TGF-β1 treatment showed no significant effects on lncRNA HAND2-AS1 expression. TGF-β1 attenuated the inhibitory effects of lncRNA HAND2-AS1 overexpression on cell migration, invasion and stemness. We concluded that lncRNA HAND2-AS1 may regulate the migration, invasion and stemness of NSCLC cells through interactions with TGF-β1.
Summary The p53 tumour-suppressor gene is found altered in the majority of colorectal cancers. Lesions include allelic loss, mutation of the gene and overexpression of the p53 protein. All of these lesions have been analysed for prognostic significance, and whereas both mutation and allelic loss have been shown to be reasonably useful markers of prognosis, the utility of overexpression of the p53 protein is more ambiguous.Given that many authors use p53 overexpression as a marker for point mutation this issue is of some importance. We have therefore examined 100 colorectal carcinomas for mutation of the p53 gene, as well as overexpression of the p53 protein. Results show that whereas mutation of the p53 gene is associated with p53 overexpression, the degree of association depends, at least in part, upon the particular antibody used. Moreover, although mutation of the p53 gene does provide prognostic information, overexpresssion of the p53 protein, as detected with two antibodies, does not. These results suggest that immunohistochemistry is not a suitable alternative to direct detection of mutations in assessing prognosis in colorectal cancer patients.
The theory of acupoint specificity is the basis for elucidating the actions of acupoints as employed in clinical practice. Acupoint specificity has become a focus of attention in international research efforts by scholars in the areas of acupuncture and moxibustion. In 2006, the Chinese Ministry of Science approved and initiated the National Basic Research Program (973 Program), one area of which was entitled Basic Research on Acupoint Specificity Based on Clinical Efficacy. Using such approaches as data mining, evidence-based medicine, clinical epidemiology, neuroimaging, molecular biology, neurophysiology, and metabolomics, fruitful research has been conducted in the form of literature research, clinical assessments, and biological studies. Acupoint specificity has been proved to exist, and it features meridian-propagated, relative, persistent, and conditional effects. Preliminarily investigations have been made into the biological basis for acupoint specificity.
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